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Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogen...

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Autores principales: Wang, Wen-Jie, Li, Hong-Tao, Yu, Jian-Ping, Li, Yu-Min, Han, Xiao-Peng, Chen, Peng, Yu, Wen-Wen, Chen, Wei-Kai, Jiao, Zuo-Yi, Liu, Hong-Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172374/
https://www.ncbi.nlm.nih.gov/pubmed/30221743
http://dx.doi.org/10.3892/mmr.2018.9457
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author Wang, Wen-Jie
Li, Hong-Tao
Yu, Jian-Ping
Li, Yu-Min
Han, Xiao-Peng
Chen, Peng
Yu, Wen-Wen
Chen, Wei-Kai
Jiao, Zuo-Yi
Liu, Hong-Bin
author_facet Wang, Wen-Jie
Li, Hong-Tao
Yu, Jian-Ping
Li, Yu-Min
Han, Xiao-Peng
Chen, Peng
Yu, Wen-Wen
Chen, Wei-Kai
Jiao, Zuo-Yi
Liu, Hong-Bin
author_sort Wang, Wen-Jie
collection PubMed
description Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet-derived growth factor receptor α (PDGFRA) wild-type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild-type GIST samples compared with KIT/PDGFRA mutant GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was conducted using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology-Based Annotation System (KOBAS) online tools, respectively. Protein-protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub-networks using the Molecular Complex Detection (MCODE) plug-in. Furthermore, enrichment analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were identified, including 238 upregulated genes primarily enriched in ‘cell adhesion’, ‘biological adhesion’, ‘cell-cell signaling’, ‘PI3K-Akt signaling pathway’ and ‘ECM-receptor interaction’, while the 308 downregulated genes were predominantly involved in ‘inflammatory response’, ‘sterol metabolic process’ and ‘fatty acid metabolic process’, ‘small GTPase mediated signal transduction’, ‘cAMP signaling pathway’ and ‘proteoglycans in cancer’. A total of 25 hub genes were obtained and four modules were mined from the PPI network, and sub-networks also revealed these genes were primarily involved in significant pathways, including ‘PI3K-Akt signaling pathway’, ‘proteoglycans in cancer’, ‘pathways in cancer’, ‘Rap1 signaling pathway’, ‘ECM-receptor interaction’, ‘phospholipase D signaling pathway’, ‘ras signaling pathway’ and ‘cGMP-PKG signaling pathway’. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild-type GISTs, including phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit γ, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb-B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results.
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spelling pubmed-61723742018-10-19 Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis Wang, Wen-Jie Li, Hong-Tao Yu, Jian-Ping Li, Yu-Min Han, Xiao-Peng Chen, Peng Yu, Wen-Wen Chen, Wei-Kai Jiao, Zuo-Yi Liu, Hong-Bin Mol Med Rep Articles Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet-derived growth factor receptor α (PDGFRA) wild-type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild-type GIST samples compared with KIT/PDGFRA mutant GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was conducted using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology-Based Annotation System (KOBAS) online tools, respectively. Protein-protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub-networks using the Molecular Complex Detection (MCODE) plug-in. Furthermore, enrichment analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were identified, including 238 upregulated genes primarily enriched in ‘cell adhesion’, ‘biological adhesion’, ‘cell-cell signaling’, ‘PI3K-Akt signaling pathway’ and ‘ECM-receptor interaction’, while the 308 downregulated genes were predominantly involved in ‘inflammatory response’, ‘sterol metabolic process’ and ‘fatty acid metabolic process’, ‘small GTPase mediated signal transduction’, ‘cAMP signaling pathway’ and ‘proteoglycans in cancer’. A total of 25 hub genes were obtained and four modules were mined from the PPI network, and sub-networks also revealed these genes were primarily involved in significant pathways, including ‘PI3K-Akt signaling pathway’, ‘proteoglycans in cancer’, ‘pathways in cancer’, ‘Rap1 signaling pathway’, ‘ECM-receptor interaction’, ‘phospholipase D signaling pathway’, ‘ras signaling pathway’ and ‘cGMP-PKG signaling pathway’. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild-type GISTs, including phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit γ, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb-B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results. D.A. Spandidos 2018-11 2018-09-05 /pmc/articles/PMC6172374/ /pubmed/30221743 http://dx.doi.org/10.3892/mmr.2018.9457 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Wen-Jie
Li, Hong-Tao
Yu, Jian-Ping
Li, Yu-Min
Han, Xiao-Peng
Chen, Peng
Yu, Wen-Wen
Chen, Wei-Kai
Jiao, Zuo-Yi
Liu, Hong-Bin
Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis
title Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis
title_full Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis
title_fullStr Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis
title_full_unstemmed Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis
title_short Identification of key genes and associated pathways in KIT/PDGFRA wild-type gastrointestinal stromal tumors through bioinformatics analysis
title_sort identification of key genes and associated pathways in kit/pdgfra wild-type gastrointestinal stromal tumors through bioinformatics analysis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172374/
https://www.ncbi.nlm.nih.gov/pubmed/30221743
http://dx.doi.org/10.3892/mmr.2018.9457
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